The major objective of this project is to study the cellular and molecular events associated with the differentiation of normal and malignant human lymphoid progenitor cells (LPC). The study will emphasize the clonal expansion of progenitor cells in non-T, non-B acute lymphoblastic leukemia (ALL) and their nonmalignant counterparts present in bone marrow (BM). Emphasis will be placed on the use of three monoclonal antibodies recently produced in our laboratory, designated BA-1, BA-2 and BA-3, that appear to bind to normal and malignant LPC at various stages of lymphoid cell development. Three specific aims are being pursued. (1)\A large number of lymphohematopoietic cell sources have been analyzed to determine the relationship between the aforementioned monoclonal antibodies and two intracellular markers of LPC, i.e., terminal deoxynucleotidyl transferase (TdT) and cytoplasmic IgM (CIgM). The cell populations were assayed by single or double fluorochrome staining, using fluorescent microscopy and flow cytofluorimetry. The results of these studies, which identified candidate lymphoid progenitor cells, have been published. (2)\The phorbol ester TPA has been used to study the induction of differentiation in normal and malignant LPC. TPA-induced changes were analyzed by immunofluorescence and biosynthetic labeling followed by SDS-PAGE. We have attempted to determine if there is a sequential (differentiation-linked?) expression of cell surface structures recognized by monoclonal antibodies, and their relationship to the intracellular markers of LPC, i.e., TdT and CIgM. The results suggest that acquisition/ loss of certain markers may be consistent with differentiation-linked events in lymphoid cell precursors. (3)\We are continuing to produce monoclonal antibodies recognizing cell surface structures on LPC that we hypothesize are part of the B-lymphocyte lineage.